Subtyping of COVID-19 samples based on cell-cell interaction in single cell transcriptomes.

In single-cell transcriptome analysis, numerous biomarkers related to COVID-19 severity, including cell subtypes, genes, and pathways, have been identified. Nevertheless, most studies have focused on severity groups based on clinical features, neglecting immunological heterogeneity within the same severity level. In this study, we employed sample-level clustering using cell-cell interaction scores to investigate patient heterogeneity and uncover novel subtypes. The clustering results were validated using external datasets, demonstrating superior reproducibility and purity compared to gene expression- or gene set enrichment-based clustering. Furthermore, the cell-cell interaction score-based clusters exhibited a strong correlation with the WHO ordinal severity score based on clinical characteristics. By characterizing the identified subtypes through known COVID-19 severity-associated biomarkers, we discovered a "Severe-like moderate" subtype. This subtype displayed clinical features akin to moderate cases; however, molecular features, such as gene expression and cell-cell interactions, resembled those of severe cases. Notably, all patients who progressed from moderate to severe belonged to this subtype, underscoring the significance of cell-cell interactions in COVID-19 patient heterogeneity and severity.

MOPA: An integrative multi-omics pathway analysis method for measuring omics activity.

Pathways are composed of proteins forming a network to represent specific biological mechanisms and are often used to measure enrichment scores based on a list of genes in means to measure their biological activity. The pathway analysis is a de facto standard downstream analysis procedure in most genomic and transcriptomic studies. Here, we present MOPA (Multi-Omics Pathway Analysis), which is a multi-omics integrative method that scores individual pathways in a sample wise manner in terms of enriched multi-omics regulatory activity, which we refer to mES (multi-omics Enrichment Score). The mES score reflects the strength of regulatory relations between multi-omics in units of pathways. In addition, MOPA is able to measure how much each omics contribute to mES that may be used to observe what kind of omics are active in a pathway within a sample group (e.g., subtype, gender), which we refer to OCR (Omics Contribution Rate). Using nine different cancer types, 93 clinical features and three types of omics (i.e., gene expression, miRNA and methylation), MOPA was used to search for clinical features that were explainable in context of multi-omics. By evaluating the performance of MOPA, we showed that it yielded higher or at least equal performance compared to previous single and multi-omics pathway analysis tools. We find that the advantage of MOPA is the ability to explain pathways in terms of omics relation using mES and OCR. As one of the results, the TGF-beta signaling pathway was captured as an important pathway that showed distinct mES and OCR values specific to the CMS4 subtype in colon adenocarcinoma. The mES and OCR metrics suggested that the mRNA and miRNA expressions were significantly different from the other subtypes, which was concordant with previous studies. The MOPA software is available at https://github.com/jaeminjj/MOPA.

Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents.

Hypomethylating agents (HMAs), such as azacitidine and decitabine, induce cancer cell death by demethylating DNAs to promote the expression of tumor-suppressor genes. HMAs also reactivate the transcription of endogenous double-stranded RNAs (dsRNAs) that trigger the innate immune response and subsequent apoptosis via viral mimicry. However, the expression patterns of endogenous dsRNAs and their relevance in the efficacy of HMAs remain largely uninvestigated. Here, we employ amidine-conjugated spiropyran (Am-SP) to examine the dynamic expression pattern of total dsRNAs regulated by HMAs. By analyzing the bone-marrow aspirates of myelodysplastic syndrome or acute myeloid leukemia patients who received the HMAs, we find a dramatic increase in total dsRNA levels upon treatment only in patients who later benefited from the therapy. We further apply our approach in solid tumor cell lines and show that the degree of dsRNA induction correlates with the effectiveness of decitabine in most cases. Notably, when dsRNA induction is accompanied by increased expression of nc886 RNA, decitabine becomes ineffective. Collectively, our study establishes the potential application of monitoring the total dsRNA levels by a small molecule as an analytical method and a dynamic marker to predict the clinical outcome of the HMA therapy.

Sinus pause during nerve integrity monitoring tube insertion following anesthetic induction with a low-dose neuromuscular blocking agent: A CARE-compliant case report.

RATIONALE: Nerve integrity monitoring (NIM) tubes are commonly used in thyroid surgery to prevent recurrent laryngeal nerve injury. To achieve the optimal electromyographic signal for NIM as intraoperative neural monitoring (IONM), the neuromuscular blocking agent (NMBA) dose should be low. The use of a low-dose NMBA increases the anesthetic and analgesic agent dose required to attenuate the laryngeal reflex during intubation. In addition, since the NMBA onset time is delayed, depending on the situation, anesthesia may become excessively deep or shallow before intubation. PATIENTS CONCERN: A 51-year-old woman scheduled for thyroid lobectomy received 0.3 mg/kg of rocuronium. Three minutes later, when the NIM tube was inserted through the vocal cord, the patient's heart rate (HR) was undetectable for 2 seconds. DIAGNOSIS: We suspected that the use of a high-dose anesthetic agent and remifentanil or the laryngocardiac reflex induced the sinus pause. INTERVENTIONS: To maintain the anesthetic depth, we administered 6 vol% of desflurane. Because the patient's systolic blood pressure was 70 mmHg and HR was 30 beats/min, we discontinued the remifentanil infusion and administered 8 mg of ephedrine. OUTCOMES: The patient's vital signs recovered to normal levels. Subsequently, there were no episodes of bradycardia or arrhythmia. CONCLUSION: Sinus pause or severe bradycardia may occur due to the laryngocardiac reflex or the administration of a high-dose anesthetic and analgesic agent during tracheal intubation in patients who received a low-dose NMBA for IONM induction using an NIM tube. Anesthesiologists should be aware of these risks and take precautions to maintain adequate anesthesia, be prepared to administer vasoactive drugs to increase the blood pressure and HR if needed, and, if possible, intravenously administer lidocaine to attenuate the laryngeal reflex during intubation.

The change of prevalence and recurrence of acute otitis media in Korea.

OBJECTIVES: Acute otitis media (AOM) is the most common infectious disease in infants and children. However, there have been few studies on the recent prevalence and trends of pediatric AOM in Korea. This study aimed to evaluate the prevalence and trends of pediatric AOM in Korea. METHODS: The data for patients with AOM in 2012, 2015, and 2017 were extracted from the Health Insurance Review and Assessment Service's Big Database. The prevalence rate, recurrence rate, and data on gender, region, month, and medical facilities of AOM were evaluated. RESULTS: The prevalence rate (per 1000 persons) decreased from 152.7 in 2012 to 137.4 in 2017. The recurrence rate declined from 34.0% in 2012 to 28.2% in 2015. In 2015, the recurrence rate of 0-2 years group decreased significantly. In 2017, the prevalence of AOM of 3-6 years group decreased the most. The prevalence is higher in urban areas and recurrence rate is higher in rural areas. But those are no significant difference. AOM is more common in male, mainly in winter and spring. CONCLUSIONS AND SIGNIFICANCE: The prevalence and recurrence rate of pediatric AOM in Korea are gradually decreasing. The decrease of prevalence resulted from declination in AOM recurrence of 0-2 years group in 2015 and AOM occurrence of 3-6 years group in 2017.

Association Between Hearing Loss and Postural Instability in Older Korean Adults.

Importance: Hearing loss is one of the most frequently occurring sensory disabilities worldwide. The association between hearing loss and postural instability in an older population remains to be studied. Objective: To determine whether the odds of postural instability increase with the degree of hearing loss and to suggest criteria for hearing rehabilitation for postural instability. Design, Setting, and Participants: This cross-sectional population-based study of 3864 participants 40 years and older with hearing loss used data from 2010 through 2012 in the fifth edition of the Korea National Health and Nutrition Examination Survey, a nationwide survey of South Korea. Pure tone audiometry was performed on both the left and right sides and each hearing grade of each side was classified into 1 of 3 subcategories: normal hearing, mild hearing loss, or moderate hearing loss (moderate hearing loss or worse). Postural instability was defined as the failure to remain standing on a foam pad surface with feet 10 cm apart with arms folded and hands cupping the elbows and eyes closed. A binomial logistic regression model was used to assess the association between hearing loss and postural instability. Data were analyzed from August 18, 2019, to September 2, 2019. Exposures: Age-related hearing loss defined as a threshold of 26 dB or more. Main Outcomes and Measures: The degree of hearing loss and postural instability. Results: Of the 3864 participants included in the study, the mean (SD) age was 57.8 (11.3) years and 2135 (55.2%) were women. Female sex was associated with higher odds of postural instability compared with male sex (odds ratio [OR], 1.65; 95% CI, 1.12-2.42, adjusted for age and hearing status), and the odds of postural instability increased with every 1 year increase in age (OR, 1.13; 95% CI, 1.10-1.16, adjusted for sex and hearing status). Unilateral or bilateral mild hearing loss was not associated with an increase in the odds of postural instability, but moderate hearing loss present on at least 1 side was associated with an increase in the odds of postural instability: unilateral moderate hearing loss group (OR, 2.71; 95% CI, 1.12-6.10, adjusted for age and sex), one mild and the other moderate hearing loss group (OR, 2.18; 95% CI, 1.16-4.09, adjusted for age and sex), and bilateral moderate hearing loss group (OR, 2.34; 95% CI, 1.27-4.33, adjusted for age and sex). Conclusions and Relevance: Aging, female sex, and having hearing loss were associated with postural instability in this analysis. Moderate or worse hearing loss present on at least 1 side was associated with increased odds of postural instability. Future research in this area is warranted to identify more precise interrelationships and preventive measures.

Aramid Nanofiber Templated In Situ SNAr Polymerization for Maximizing the Performance of All-Organic Nanocomposites.

The performance limits of conventional super engineering plastics with inorganic nanofillers are surpassed by all-organic nanocomposites prepared via in situ SNAr polymerization of polysulfone (PSU) in the presence of a highly dispersed aramid nanofiber (ANF) solution. The latter is directly used, bypassing the energy-consuming, nanostructure-damaging workup process. Using only a 0.15 wt % nanofiller, the all-organic nanocomposite shows an ultimate tensile strength 1.6× higher and 3.4× tougher than neat PSU and its blending counterpart due to the mutually interactive filler and maximally homogenized matrix. The exceptional toughness of the ANF/PSU nanocomposite originates from the grafted PSU on the surface of ANF; it drives stress-delocalized deformation, as revealed by stress-absorbable viscoelastic behavior and ductile elongation of materials. This material is a promising candidate for use as a filler-interactive, high-performance nanocomposite.